Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
| Autor: | Paul Rooney, Christopher R. Fellows, Kajal Gohil, Rebecca Williams, Ilyas M. Khan, Iwan Davies, Charles W. Archer, John A. Fairclough, Duncan M. Baird |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Senescence Adult Cartilage Articular Cell Separation Biology Article 03 medical and health sciences 0302 clinical medicine Osteoarthritis medicine Chromosomes Human Humans Progenitor cell Cellular Senescence Progenitor Aged 030203 arthritis & rheumatology Aged 80 and over Cell Nucleus Multidisciplinary Cluster of differentiation Cartilage Stem Cells Mesenchymal stem cell Middle Aged Telomere beta-Galactosidase R1 Phenotype Cell biology Clone Cells Adult Stem Cells 030104 developmental biology medicine.anatomical_structure Bromodeoxyuridine Immunology Linear Models |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | In recent years it has become increasingly clear that articular cartilage harbours a viable pool of progenitor cells and interest has focussed on their role during development and disease. Analysis of progenitor numbers using fluorescence-activated sorting techniques has resulted in wide-ranging estimates, which may be the result of context-dependent expression of cell surface markers. We have used a colony-forming assay to reliably determine chondroprogenitor numbers in normal and osteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P 0.0001). Intriguingly, cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilage revealed the presence of a divergent progenitor subpopulation characterised by an early senescent phenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidase activity, lower average telomere lengths but retained the capacity to undergo multi-lineage differentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be a significant component of the pathological process. This study shows that although early senescence is an inherent property of a subset of activated progenitors, there is also a pool of progenitors with extended viability and regenerative potential residing within osteoarthritic cartilage. |
| Databáze: | OpenAIRE |
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